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【结 构 式】 
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【分子编号】44145 【品名】4-[hydroxy(3-nitrophenyl)methyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide 【CA登记号】 |
【 分 子 式 】C12H14N4O5S 【 分 子 量 】326.33312 【元素组成】C 44.17% H 4.32% N 17.17% O 24.51% S 9.83% |
合成路线1
该中间体在本合成路线中的序号：(III)Treatment of 4-iodo-N,N-dimethyl-1H-imidazole-1-sulfonamide (I) with EtMgBr and 3-nitrobenzaldehyde (II) in CH2Cl2 yields derivative (III), whose nitro moiety is reduced by hydrogenation over Pd/C in EtOAc to afford aminophenyl derivative (IV). Treatment of (IV) with Et3SiH in TFA provides aminobenzyl derivative (V), which is finally converted into the desired compound by treatment with pyridine and ethanesulfonyl chloride (VI) followed by reflux in HCl.
| 【1】 Altenbach, R.J.; Holladay, M.W.; Carroll, W.A.; Meyer, M.D.; Kerwin, J.F. Jr.; Kolasa, T.; Rohde, J.; Khilevich, A. (Abbott Laboratories Inc.); Imidazoles and related cpds. as alpha1A agonists. WO 0007997 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 44143 | 4-iodo-N,N-dimethyl-1H-imidazole-1-sulfonamide | C5H8IN3O2S | 详情 | 详情 | |
| (II) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (III) | 44145 | 4-[hydroxy(3-nitrophenyl)methyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C12H14N4O5S | 详情 | 详情 | |
| (IV) | 44146 | 4-[(3-aminophenyl)(hydroxy)methyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C12H16N4O3S | 详情 | 详情 | |
| (V) | 44147 | 4-(3-aminobenzyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide | C12H16N4O2S | 详情 | 详情 | |
| (VI) | 54065 | Ethanesulfonyl chloride; Ethylsulfonyl chloride | 594-44-5 | C2H5ClO2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The condensation of 4-iodo-N,N-dimethyl-1H-imidazole-1-sulfonamide (I) with 3-nitrobenzaldehyde (II) by means of Et-MgBr in dichloromethane gives the carbinol (III), which is reduced with triethylsilane in refluxing TFA to yield 4-(3-nitrobenzyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (IV). The reduction of the nitro group of (IV) by means of H2 over Pd/C in ethyl acetate affords the amino derivative (V), which is acylated with ethanesulfonyl chloride (VI) and pyridine in dichloromethane to give the ethanesulfonamide (VII). Finally, this compound is treated with aqueous refluxing HCl to yield the target compound.
| 【1】 Khilevich, A.; Altenbach, R.J.; Meyer, M.D.; et al.; N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel alpha1-adrenoceptor ligand with an enhanced in vitro and in vivo profile relative to phenylpropanolamine and midodrine. J Med Chem 2002, 45, 20, 4395. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 44143 | 4-iodo-N,N-dimethyl-1H-imidazole-1-sulfonamide | C5H8IN3O2S | 详情 | 详情 | |
| (II) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (III) | 44145 | 4-[hydroxy(3-nitrophenyl)methyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C12H14N4O5S | 详情 | 详情 | |
| (IV) | 58281 | N,N-dimethyl-4-(3-nitrobenzyl)-1H-imidazole-1-sulfonamide | C12H14N4O4S | 详情 | 详情 | |
| (V) | 44147 | 4-(3-aminobenzyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide | C12H16N4O2S | 详情 | 详情 | |
| (VI) | 54065 | Ethanesulfonyl chloride; Ethylsulfonyl chloride | 594-44-5 | C2H5ClO2S | 详情 | 详情 |
| (VII) | 58282 | 4-{3-[(ethylsulfonyl)amino]benzyl}-N,N-dimethyl-1H-imidazole-1-sulfonamide | C14H20N4O4S2 | 详情 | 详情 |